Sanford Children's Health Research Center, Sanford Research USD, Sioux Falls, South Dakota, USA.
J Neurosci Res. 2013 Sep;91(9):1117-32. doi: 10.1002/jnr.23238. Epub 2013 May 17.
Congenital hydrocephalus is a relatively common and debilitating birth defect with several known physiological causes. Dysfunction of motile cilia on the ependymal cells that line the ventricular surface of the brain can result in hydrocephalus by hindering the proper flow of cerebrospinal fluid. As a result, hydrocephalus can be associated with primary ciliary dyskinesia, a rare pediatric syndrome resulting from defects in ciliary and flagellar motility. Although the prevalence of hydrocephalus in primary ciliary dyskinesia patients is low, it is a common hallmark of the disease in mouse models, suggesting that distinct genetic mechanisms underlie the differences in the development and physiology of human and mouse brains. Mouse models of primary ciliary dyskinesia reveal strain-specific differences in the appearance and severity of hydrocephalus, indicating the presence of genetic modifiers segregating in inbred strains. These models may provide valuable insight into the genetic mechanisms that regulate susceptibility to hydrocephalus under the conditions of ependymal ciliary dysfunction.
先天性脑积水是一种相对常见且使人虚弱的出生缺陷,其具有多种已知的生理病因。脑室内表面的室管膜细胞上的活动纤毛功能障碍会阻碍脑脊液的正常流动,从而导致脑积水。因此,脑积水可能与原发性纤毛运动障碍有关,这是一种罕见的儿科综合征,由纤毛和鞭毛运动缺陷引起。尽管原发性纤毛运动障碍患者的脑积水患病率较低,但它是小鼠模型中该疾病的常见特征,这表明人类和小鼠大脑的发育和生理学差异存在不同的遗传机制。原发性纤毛运动障碍的小鼠模型揭示了在脑积水的出现和严重程度上存在特定于品系的差异,这表明存在遗传修饰因子在近交系中分离。这些模型可能为研究在室管膜纤毛功能障碍的情况下调节脑积水易感性的遗传机制提供有价值的见解。